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Biomedical subjects

Paul M Thompson

Publications and source records attributed to Paul M Thompson.

At least 73 records · Page 4Linked to original sources
PubMed2005

Genetics of brain structure and intelligence.

Genetic influences on brain morphology and IQ are well studied. A variety of sophisticated brain-mapping approaches relating genetic influences on brain structure and intelligence establishes a regional distribution for this relationship that is consistent with behavioral studies. We highlight those studies that illustrate the complex cortical patterns associated with measures of cognitive ability. A measure of cognitive ability, known as g, has been shown highly heritable across many studies. We argue that these genetic links are partly mediated by brain structure that is likewise under strong genetic control. Other factors, such as the environment, obviously play a role, but the predominant determinant appears to be genetic.

Animals↗
PubMed2004

Longitudinal mapping of cortical thickness and brain growth in normal children.

Recent advances in magnetic resonance imaging (MRI) technology now allow the tracing of developmental changes in the brains of children. We applied computer-matching algorithms and new techniques for measuring cortical thickness (in millimeters) to the structural MRI images of 45 children scanned twice (2 yr apart) between the ages 5 and 11. Changes in brain size were also assessed, showing local brain growth progressing at a rate of approximately 0.4-1.5 mm per year, most prominently in frontal and occipital regions. Estimated cortical thickness ranged from 1.5 mm in occipital regions to 5.5 mm in dorsomedial frontal cortex. Gray matter thinning coupled with cortical expansion was highly significant in right frontal and bilateral parieto-occipital regions. Significant thickening was restricted to left inferior frontal (Broca's area) and bilateral posterior perisylvian (Wernicke's area on the left) regions. In the left hemisphere, gray matter thickness was correlated with changing cognitive abilities. For the first time, developmental changes in gray matter thickness, brain size, and structure-function relationships have been traced within the same individuals studied longitudinally during a time of rapid cognitive development.

Adult↗
PubMed2004

Mapping cortical thickness and gray matter concentration in first episode schizophrenia.

We mapped regional changes in cortical thickness and intensity-based cortical gray matter concentration in first episode schizophrenia. High-resolution magnetic resonance images were obtained from 72 (51 male, 21 female) first episode patients and 78 (37 male, 41 female) healthy subjects similar in age. Cortical pattern matching methods allowed comparisons of cortical thickness and gray matter concentration at thousands of homologous cortical locations between subjects in three dimensions. Principal components analyses reduced measures obtained across the cortex to identify global differences in cortical thickness/gray matter concentration. First principal component factor scores showed significant effects of diagnosis, sex and age for both cortical measures. Diagnosis and age effects remained significant after brain size correction. Cortical thickness and gray matter concentration values were highly correlated. Statistical maps showed significant regional gray matter thinning in frontal, temporal and parietal heteromodal association cortices bilaterally in first episode patients. Regional reductions in cortical gray matter concentration were similar but pronounced in the superior temporal lobe. Regional reductions in cortical thickness and gray matter concentration are present at disease onset in brain regions linked with functional disturbances in schizophrenia. Cortical thickness and gray matter concentration mapping produce similar results, although the concentration metric may be influenced by diagnostic differences in extra-cortical cerebrospinal fluid and surface curvature/complexity.

Adult↗
PubMed2004

Structural abnormalities in the brains of human subjects who use methamphetamine.

We visualize, for the first time, the profile of structural deficits in the human brain associated with chronic methamphetamine (MA) abuse. Studies of human subjects who have used MA chronically have revealed deficits in dopaminergic and serotonergic systems and cerebral metabolic abnormalities. Using magnetic resonance imaging (MRI) and new computational brain-mapping techniques, we determined the pattern of structural brain alterations associated with chronic MA abuse in human subjects and related these deficits to cognitive impairment. We used high-resolution MRI and surface-based computational image analyses to map regional abnormalities in the cortex, hippocampus, white matter, and ventricles in 22 human subjects who used MA and 21 age-matched, healthy controls. Cortical maps revealed severe gray-matter deficits in the cingulate, limbic, and paralimbic cortices of MA abusers (averaging 11.3% below control; p < 0.05). On average, MA abusers had 7.8% smaller hippocampal volumes than control subjects (p < 0.01; left, p = 0.01; right, p < 0.05) and significant white-matter hypertrophy (7.0%; p < 0.01). Hippocampal deficits were mapped and correlated with memory performance on a word-recall test (p < 0.05). MRI-based maps suggest that chronic methamphetamine abuse causes a selective pattern of cerebral deterioration that contributes to impaired memory performance. MA may selectively damage the medial temporal lobe and, consistent with metabolic studies, the cingulate-limbic cortex, inducing neuroadaptation, neuropil reduction, or cell death. Prominent white-matter hypertrophy may result from altered myelination and adaptive glial changes, including gliosis secondary to neuronal damage. These brain substrates may help account for the symptoms of MA abuse, providing therapeutic targets for drug-induced brain injury.

Adult↗
PubMed2004

Dynamic mapping of human cortical development during childhood through early adulthood.

We report the dynamic anatomical sequence of human cortical gray matter development between the age of 4-21 years using quantitative four-dimensional maps and time-lapse sequences. Thirteen healthy children for whom anatomic brain MRI scans were obtained every 2 years, for 8-10 years, were studied. By using models of the cortical surface and sulcal landmarks and a statistical model for gray matter density, human cortical development could be visualized across the age range in a spatiotemporally detailed time-lapse sequence. The resulting time-lapse "movies" reveal that (i) higher-order association cortices mature only after lower-order somatosensory and visual cortices, the functions of which they integrate, are developed, and (ii) phylogenetically older brain areas mature earlier than newer ones. Direct comparison with normal cortical development may help understanding of some neurodevelopmental disorders such as childhood-onset schizophrenia or autism.

Adolescent↗
PubMed2004

Abnormal gyral complexity in first-episode schizophrenia.

BACKGROUND: Abnormalities in the patterns and frequency of cortical folding might help identify temporal and regionally specific disturbances in normal neurodevelopmental processes that occur in association with schizophrenia. Few studies, however, have investigated gyral complexity in schizophrenia. METHODS: High-resolution magnetic resonance images were used to examine differences in gyral complexity, measured three-dimensionally in five separate hemispheric regions covering the entire cortical surface, in patients with first-episode schizophrenia (n = 50) compared with demographically matched healthy comparison subjects (n = 50). The modulating effects of gender and hemisphere were also examined. RESULTS: Significant increases in cortical folding were observed in the right superior frontal cortex in male schizophrenic patients compared with male control subjects, but not between female diagnostic groups. Significant main effects of hemisphere were found in frontal, parietal, and occipital regions in directions complementary to cerebral torques. CONCLUSIONS: Results support previous findings of right frontal hypergyria in male schizophrenic patients and suggest that these abnormalities predate illness onset and are of neurodevelopmental origin. Therefore, in schizophrenia, sexually dimorphic developmental processes and differences in hemispheric connectivity, which have been shown to influence the organization and/or frequency of cortical folding, seem to be disturbed during gyral formation in utero.

Adult↗
PubMed2004

Mapping brain size and cortical gray matter changes in elderly depression.

BACKGROUND: In elderly depression, volumetric brain imaging findings suggest abnormalities of the frontal lobe, particularly the orbitofrontal cortex, and the hippocampus. No studies to date have mapped cortical abnormalities over the entire brain surface in major depression. Here, we conducted detailed spatial analyses of brain size and gray matter within the cortical mantle in elderly patients with major depression. METHODS: High-resolution, three-dimensional, structural magnetic resonance imaging data and cortical pattern matching methods were used in 24 depressed elderly patients and 19 group-matched controls to measure local brain size and proportions of gray matter at thousands of homologous cortical surface locations. RESULTS: Prominent brain size reductions were observed in the depressed subjects in the orbitofrontal cortex bilaterally. Cortical gray matter measurements revealed significant gray matter increases in the orbitofrontal cortex, adjacent to focal trend level significant decreases of gray matter in the same region. Depressed patients also exhibited significant gray matter increases in parietal cortices, as well as the left temporal cortex. CONCLUSIONS: Complex cortical changes may contribute to the brain size reduction of the orbitofrontal cortex and to the gray matter abnormalities detected in orbitofrontal cortex and temporoparietal cortices, thereby providing a potentially new window into the pathophysiology of elderly depression.

Aged↗
PubMed2004

Regional specificity of hippocampal volume reductions in first-episode schizophrenia.

Hippocampal volume reductions are widely observed in schizophrenia. Some studies suggest anterior hippocampal regions are more susceptible and associated with frontal lobe dysfunctions, while others implicate posterior regions. Using high-resolution MR images and novel computational image analysis methods, we identified the hippocampal subregions most vulnerable to disease processes in 62 (45 m/17 f) first-episode schizophrenia patients compared to 60 (30 m/30 f) healthy controls, similar in age. The hippocampi were traced on coronal brain slices and hemispheric volumes were compared between diagnostic groups. Regional structural abnormalities were identified by comparing distances, measured from homologous hippocampal surface points to the central core of each individual's hippocampal surface model, between groups in 3D. CSF concentrations were also compared statistically at homologous hippocampal surface points to localize corresponding gray matter reductions. Significant bilateral hippocampal volume reductions were observed in schizophrenia irrespective of brain size corrections. Statistical mapping results, confirmed by permutation testing, showed pronounced left hemisphere shape differences in anterior and midbody CA1 and CA2 regions in patients. Significant CSF increases surrounding the hippocampus were observed in a similar spatial pattern in schizophrenia. Results confirm that hippocampal volume reductions are a robust neuroanatomical correlate of schizophrenia and are present by first episode. Mid- to antero-lateral hippocampal regions show pronounced volume changes and complementary increases in peri-hippocampal CSF, suggesting that these hippocampal regions are more susceptible to disease processes in schizophrenia. Targeting regional hippocampal abnormalities may help dissociate schizophrenia patients from other groups exhibiting global hippocampal volume changes, and better focus systems-level pathophysiological hypotheses.

Adolescent↗
PubMed2004

Gender differences in the left inferior frontal gyrus in normal children.

This study examined frontal lobe subregions in 46 normal children and adolescents (25 females, mean age: 11.08, SD: 3.07; and 21 males, mean age: 10.76, SD: 2.61) to assess the effects of age and gender on volumetric measures as well as hemispheric asymmetries. Superior, middle, inferior, and orbito-frontal gray, white, and cerebrospinal (CSF) volumes were manually delineated in high-resolution magnetic resonance imaging (MRI) data to assess possible morphological changes. We report a significant age-related increase in the white matter of the left inferior frontal gyrus (IFG) in boys (P = 0.007). Additionally, the left IFG was significantly larger in boys compared to girls (P = 0.004). Boys showed increased gray matter volume relative to girls even after correcting for total cerebral volume. Also, boys were found to have significant Right > Left asymmetry patterns with greater right hemispheric volumes for total cerebral volume, total cerebral white matter, MFG white matter, and SFG white matter (P < 0.001). Girls showed significant Right > Left asymmetry patterns in total cerebral and SFG white matter (P < 0.001). These findings suggest continued modification of the IFG during normal development in boys, and significant gender differences in IFG gray matter between boys and girls that may be possibly linked to gender differences in speech development and lateralization of language.

Age Factors↗
PubMed2004

Mapping hippocampal and ventricular change in Alzheimer disease.

We developed an anatomical mapping technique to detect hippocampal and ventricular changes in Alzheimer disease (AD). The resulting maps are sensitive to longitudinal changes in brain structure as the disease progresses. An anatomical surface modeling approach was combined with surface-based statistics to visualize the region and rate of atrophy in serial MRI scans and isolate where these changes link with cognitive decline. Sixty-two [corrected] high-resolution MRI scans were acquired from 12 AD patients (mean [corrected] age +/- SE at first scan: 68.7 +/- 1.7 [corrected] years) and 14 matched controls (age: 71.4 +/- 0.9 years) [corrected] each scanned twice (1.9 +/- 0.2 [corrected] years apart, when all subjects are pooled [corrected] 3D parametric mesh models of the hippocampus and temporal horns were created in sequential scans and averaged across subjects to identify systematic patterns of atrophy. As an index of radial atrophy, 3D distance fields were generated relating each anatomical surface point to a medial curve threading down the medial axis of each structure. Hippocampal atrophic rates and ventricular expansion were assessed statistically using surface-based permutation testing and were faster in AD than in controls. Using color-coded maps and video sequences, these changes were visualized as they progressed anatomically over time. Additional maps localized regions where atrophic changes linked with cognitive decline. Temporal horn expansion maps were more sensitive to AD progression than maps of hippocampal atrophy, but both maps correlated with clinical deterioration. These quantitative, dynamic visualizations of hippocampal atrophy and ventricular expansion rates in aging and AD may provide a promising measure to track AD progression in drug trials.

Aged↗
PubMed2004

Comparing gray matter loss profiles between dementia with Lewy bodies and Alzheimer's disease using cortical pattern matching: diagnosis and gender effects.

We used magnetic resonance imaging (MRI) and cortical pattern matching to map differences in cortical gray matter deficits between Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), and explored the possible influence of gender on these patterns. Twenty-nine patients with AD (age 77.9 +/- 5.5), 16 patients with DLB (76.4 +/- 6.7), and 38 controls (75.3 +/- 6.8) were included. Dementia groups were matched for illness severity. Detailed spatial analyses of gray matter were conducted across the entire cerebral cortex by measuring local proportions of gray matter at thousands of homologous cortical surface locations in each subject and between diagnostic groups. To visualize regional changes, statistical differences were mapped at each cortical surface location in 3D. Main effects of diagnosis demonstrated prominent gray matter differences in orbitofrontal and temporal cortices, where AD exhibited the greatest deficits relative to DLB. Main effects of sex showed less gray matter in men within all group comparisons. Exploratory findings for sex by diagnosis interactions suggest greater gray matter loss in the anterior cingulate for men with AD, relative to controls, AD females, and individuals with DLB. Relative preservation of orbitofrontal cortices in addition to temporal structures may contribute to distinguishing DLB from AD. Further investigation of the influence of gender might provide a more comprehensive understanding of the pathophysiological differences underlying the two forms of dementia.

Aged↗
PubMed2004

Expert knowledge-guided segmentation system for brain MRI.

We describe an automated 3-D segmentation system for in vivo brain magnetic resonance images (MRI). Our segmentation method combines a variety of filtering, segmentation, and registration techniques and makes maximum use of the available a priori biomedical expertise, both in an implicit and an explicit form. We approach the issue of boundary finding as a process of fitting a group of deformable templates (simplex mesh surfaces) to the contours of the target structures. These templates evolve in parallel, supervised by a series of rules derived from analyzing the template's dynamics and from medical experience. The templates are also constrained by knowledge on the expected textural and shape properties of the target structures. We apply our system to segment four brain structures (corpus callosum, ventricles, hippocampus, and caudate nuclei) and discuss its robustness to imaging characteristics and acquisition noise.

Algorithms↗
PubMed2004

Mapping cortical change in Alzheimer's disease, brain development, and schizophrenia.

This paper describes algorithms that can identify patterns of brain structure and function associated with Alzheimer's disease, schizophrenia, normal aging, and abnormal brain development based on imaging data collected in large human populations. Extraordinary information can be discovered with these techniques: dynamic brain maps reveal how the brain grows in childhood, how it changes in disease, and how it responds to medication. Genetic brain maps can reveal genetic influences on brain structure, shedding light on the nature-nurture debate, and the mechanisms underlying inherited neurobehavioral disorders. Recently, we created time-lapse movies of brain structure for a variety of diseases. These identify complex, shifting patterns of brain structural deficits, revealing where, and at what rate, the path of brain deterioration in illness deviates from normal. Statistical criteria can then identify situations in which these changes are abnormally accelerated, or when medication or other interventions slow them. In this paper, we focus on describing our approaches to map structural changes in the cortex. These methods have already been used to reveal the profile of brain anomalies in studies of dementia, epilepsy, depression, childhood- and adult-onset schizophrenia, bipolar disorder, attention-deficit/hyperactivity disorder, fetal alcohol syndrome, Tourette syndrome, Williams syndrome, and in methamphetamine abusers. Specifically, we describe an image analysis pipeline known as cortical pattern matching that helps compare and pool cortical data over time and across subjects. Statistics are then defined to identify brain structural differences between groups, including localized alterations in cortical thickness, gray matter density (GMD), and asymmetries in cortical organization. Subtle features, not seen in individual brain scans, often emerge when population-based brain data are averaged in this way. Illustrative examples are presented to show the profound effects of development and various diseases on the human cortex. Dynamically spreading waves of gray matter loss are tracked in dementia and schizophrenia, and these sequences are related to normally occurring changes in healthy subjects of various ages.

Algorithms↗
PubMed2004

Gender differences in cortical complexity.

Cortical complexity, a measure that quantifies the spatial frequency of gyrification and fissuration of the brain surface, has not been thoroughly characterized with respect to gender differences in the human brain. Using a new three-dimensional (3D) analytic technique with magnetic resonance imaging, we found greater gyrification in women than men in frontal and parietal regions. Increased complexity implies more cortical surface area, which may offset gender differences in brain volume and account for behavioral gender differences.

Cerebral Cortex↗
PubMed2004

Campylobacter insulaenigrae sp. nov., isolated from marine mammals.

Phenotypic and phylogenetic studies were performed on four Campylobacter-like organisms recovered from three seals and a porpoise. Comparative 16S rRNA gene sequencing studies demonstrated that the organisms represent a hitherto unknown subline within the genus Campylobacter, associated with a subcluster containing Campylobacter jejuni, Campylobacter coli and Campylobacter lari. DNA-DNA hybridization studies confirmed that the bacteria belonged to a single species, for which the name Campylobacter insulaenigrae sp. nov. is proposed. The type strain of Campylobacter insulaenigrae sp. nov. is NCTC 12927(T) (=CCUG 48653(T)).

Animals↗
PubMed2004

An adaptive level set segmentation on a triangulated mesh.

Level set methods offer highly robust and accurate methods for detecting interfaces of complex structures. Efficient techniques are required to transform an interface to a globally defined level set function. In this paper, a novel level set method based on an adaptive triangular mesh is proposed for segmentation of medical images. Special attention is paid to an adaptive mesh refinement and redistancing technique for level set propagation, in order to achieve higher resolution at the interface with minimum expense. First, a narrow band around the interface is built in an upwind fashion. An active square technique is used to determine the shortest distance correspondence (SDC) for each grid vertex. Simultaneously, we also give an efficient approach for signing the distance field. Then, an adaptive improvement algorithm is proposed, which essentially combines two basic techniques: a long-edge-based vertex insertion strategy, and a local improvement. These guarantee that the refined triangulation is related to features along the front and has elements with appropriate size and shape, which fit the front well. We propose a short-edge elimination scheme to coarsen the refined triangular mesh, in order to reduce the extra storage. Finally, we reformulate the general evolution equation by updating 1) the velocities and 2) the gradient of level sets on the triangulated mesh. We give an approach for tracing contours from the level set on the triangulated mesh. Given a two-dimensional image with N grids along a side, the proposed algorithms run in O(kN) time at each iteration. Quantitative analysis shows that our algorithm is of first order accuracy; and when the interface-fitted property is involved in the mesh refinement, both the convergence speed and numerical accuracy are greatly improved. We also analyze the effect of redistancing frequency upon convergence speed and accuracy. Numerical examples include the extraction of inner and outer surfaces of the cerebral cortex from magnetic resonance imaging brain images.

Algorithms↗
PubMed2004

Genus zero surface conformal mapping and its application to brain surface mapping.

We developed a general method for global conformal parameterizations based on the structure of the cohomology group of holomorphic one-forms for surfaces with or without boundaries (Gu and Yau, 2002), (Gu and Yau, 2003). For genus zero surfaces, our algorithm can find a unique mapping between any two genus zero manifolds by minimizing the harmonic energy of the map. In this paper, we apply the algorithm to the cortical surface matching problem. We use a mesh structure to represent the brain surface. Further constraints are added to ensure that the conformal map is unique. Empirical tests on magnetic resonance imaging (MRI) data show that the mappings preserve angular relationships, are stable in MRIs acquired at different times, and are robust to differences in data triangulation, and resolution. Compared with other brain surface conformal mapping algorithms, our algorithm is more stable and has good extensibility.

Algorithms↗